DE2166327C3 - 3,4-Dihydro-2 (1 H) -quinazolinone - Google Patents
3,4-Dihydro-2 (1 H) -quinazolinoneInfo
- Publication number
- DE2166327C3 DE2166327C3 DE19712166327 DE2166327A DE2166327C3 DE 2166327 C3 DE2166327 C3 DE 2166327C3 DE 19712166327 DE19712166327 DE 19712166327 DE 2166327 A DE2166327 A DE 2166327A DE 2166327 C3 DE2166327 C3 DE 2166327C3
- Authority
- DE
- Germany
- Prior art keywords
- quinazolinone
- dihydro
- acid
- general formula
- chloro
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
- CTOUNZIAEBIWAW-UHFFFAOYSA-N 3,4-dihydro-1h-quinazolin-2-one Chemical compound C1=CC=C2NC(=O)NCC2=C1 CTOUNZIAEBIWAW-UHFFFAOYSA-N 0.000 title claims 2
- 150000003839 salts Chemical class 0.000 claims description 6
- 239000002253 acid Substances 0.000 claims description 4
- 150000007513 acids Chemical class 0.000 claims description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 2
- 229910052757 nitrogen Inorganic materials 0.000 claims description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
- 150000001875 compounds Chemical class 0.000 description 10
- AVRPFRMDMNDIDH-UHFFFAOYSA-N 1h-quinazolin-2-one Chemical class C1=CC=CC2=NC(O)=NC=C21 AVRPFRMDMNDIDH-UHFFFAOYSA-N 0.000 description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 230000003110 anti-inflammatory effect Effects 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 239000003638 chemical reducing agent Substances 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 235000005911 diet Nutrition 0.000 description 2
- 230000000378 dietary effect Effects 0.000 description 2
- HYYBABOKPJLUIN-UHFFFAOYSA-N mefenamic acid Chemical compound CC1=CC=CC(NC=2C(=CC=CC=2)C(O)=O)=C1C HYYBABOKPJLUIN-UHFFFAOYSA-N 0.000 description 2
- 229910052987 metal hydride Inorganic materials 0.000 description 2
- 150000004681 metal hydrides Chemical class 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 239000012279 sodium borohydride Substances 0.000 description 2
- 229910000033 sodium borohydride Inorganic materials 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- MAOBFOXLCJIFLV-UHFFFAOYSA-N (2-aminophenyl)-phenylmethanone Chemical compound NC1=CC=CC=C1C(=O)C1=CC=CC=C1 MAOBFOXLCJIFLV-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- VFLYBTWSMSKOIA-UHFFFAOYSA-N 6-chloro-3-[2-(diethylamino)ethyl]-4-phenyl-1,4-dihydroquinazolin-2-one Chemical compound C12=CC(Cl)=CC=C2NC(=O)N(CCN(CC)CC)C1C1=CC=CC=C1 VFLYBTWSMSKOIA-UHFFFAOYSA-N 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 239000012448 Lithium borohydride Substances 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- LEHOTFFKMJEONL-UHFFFAOYSA-N Uric Acid Chemical compound N1C(=O)NC(=O)C2=C1NC(=O)N2 LEHOTFFKMJEONL-UHFFFAOYSA-N 0.000 description 1
- TVWHNULVHGKJHS-UHFFFAOYSA-N Uric acid Natural products N1C(=O)NC(=O)C2NC(=O)NC21 TVWHNULVHGKJHS-UHFFFAOYSA-N 0.000 description 1
- -1 alkyl isocyanate Chemical class 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 230000001760 anti-analgesic effect Effects 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 229910017052 cobalt Inorganic materials 0.000 description 1
- 239000010941 cobalt Substances 0.000 description 1
- GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000000994 depressogenic effect Effects 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 239000012948 isocyanate Substances 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 229960003464 mefenamic acid Drugs 0.000 description 1
- YDNQWVQHOZJNLQ-UHFFFAOYSA-N n-(2-benzoyl-4-chlorophenyl)-2,2,2-trichloroacetamide Chemical compound ClC1=CC=C(NC(=O)C(Cl)(Cl)Cl)C(C(=O)C=2C=CC=CC=2)=C1 YDNQWVQHOZJNLQ-UHFFFAOYSA-N 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 229910003446 platinum oxide Inorganic materials 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 150000003246 quinazolines Chemical class 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000001384 succinic acid Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 229940116269 uric acid Drugs 0.000 description 1
- 125000005853 β-dimethylaminoethyl group Chemical group 0.000 description 1
Description
2. Arzneimittel, bestehend aus einer Verbindung gemäß Anspruch 1 oder deren Salz und üblichen Trägerstoffen und/oder Verdünnungsmitteln und/ oder Hilfsstoffen.2. Medicament consisting of a compound according to claim 1 or its salt and usual Carriers and / or diluents and / or auxiliaries.
1515th
Die Erfindung betrifft 3,4-Dihydro-2(l H)-chinazolinono der allgemeinen Fonnel IThe invention relates to 3,4-dihydro-2 (1 H) -quinazolinono of the general formula I.
und Xi, X2 und X3 Halogenatome sind, reduziert und gegebenenfalls die erhaltene Verbindung mit einer Säure behandelt.and Xi, X2 and X3 are halogen atoms, reduced and optionally treating the compound obtained with an acid.
In diesem Verfahren werden die Chinazolinone der allgemeinen Formel I durch Behandlung einer Verbindung der allgemeinen Formel II mit einem Reduktionsmittel in Gegenwart eines Lösungsmittels hergestellt Beispiele für geeignete Reduktionsmittel sind komplexe Metallhydride, wie Natriumborhydrid, Lithiumborhydrid, Diisobutylaluminiumhydrid oder gemischte Metallhydride oder Wasserstoff in Gegenwart eines Katalysators, wie Nickel, Palladium, Platinoxid, Kupfer oder Kobalt Ferner können andere übliche Methoden zur Reduktion einer Kohlenstoff-Stickstoff-Doppelbindung angewandt werden.In this process, the quinazolinones of general formula I are prepared by treating a compound of the general formula II prepared with a reducing agent in the presence of a solvent Examples of suitable reducing agents are complex metal hydrides, such as sodium borohydride, lithium borohydride, Diisobutylaluminum hydride or mixed metal hydrides or hydrogen in the presence of a catalyst, Such as nickel, palladium, platinum oxide, copper or cobalt can also be used other conventional methods for Reduction of a carbon-nitrogen double bond can be applied.
Beispiele für geeignete Lösungsmittel sind Methanol, Äthanol, Isopropanol, Methylenchlorid, Chloroform, Tetrachlorkohlenstoff, Diäthyläther, Tetrahydrofuran, Dimethylformamid, Diäihy'forrnamiu, Dimethyiaceiamid, Wasser, Essigsäure und Ameisensäure. Die Umsetzung verläuft glatt bei Raumtemperatur. Erforderlichenfalls können auch höhere oder niedrigere Temperaturen angewendet werden, um die Reaktion steuern zu können.Examples of suitable solvents are methanol, ethanol, isopropanol, methylene chloride, Chloroform, carbon tetrachloride, diethyl ether, tetrahydrofuran, dimethylformamide, Diäihy'forrnamiu, Dimethyiaceiamid, water, Acetic acid and formic acid. The reaction proceeds smoothly at room temperature. If necessary, higher or lower Temperatures are used to control the reaction can.
Die Ausgangsverbindungen der allgemeinen Formel II lassen sich z. B. durch Umsetzung eines Trihalogenacetanilids der allgemeinen Formel IIIThe starting compounds of the general formula II can be, for. B. by implementing a Trihaloacetanilide of the general formula III
>-ii"2ii '> -ii "2ii '
R2 R 2
(D(D
C=N-CnH2n-NC = NC n H 2n -N
X1 (H)X 1 (H)
NH-CO —C-X,NH-CO —C-X,
3535
4545
in der η die Zahl 2 oder 3 bedeutet und Ri und R2 je eine Methyl- oder Äthylgruppe bedeuten oder zusammen mit dem Stickstoffatom, an das sie gebunden sind, «ine Morpholinogruppe bilden, und ihre Salze mit Säuren.in which η denotes the number 2 or 3 and Ri and R 2 each denote a methyl or ethyl group or, together with the nitrogen atom to which they are attached, form a morpholino group and their salts with acids.
Es sind einige Verfahren zur Herstellung von ähnlichen Chinazolinonen bekannt. Beispielsweise werden diese Verbindungen durch Umsetzung eines 2-Aminobenzophenons mit einem Alkylisocyanat und Reduktion des erhaltenen 3-Alkyl-2(3H)-chinazolinons hergestellt; vgl. W. M e 11 e s i c s et al„ J. Org. Chem., Bd. 31 (1966), S. 1007.Several methods of making similar quinazolinones are known. For example be these compounds by reacting a 2-aminobenzophenone with an alkyl isocyanate and Reduction of the obtained 3-alkyl-2 (3H) -quinazolinone prepared; cf. W. M e 11 e s i c s et al "J. Org. Chem., Vol. 31 (1966), p. 1007.
Im Gegensatz zu dem bekannten Verfahren können die neuen Chinazolinone der allgemeinen Formel I glatt und wirtschaftlich und in hoher Ausbeute und Reinheit dadurch hergestellt werden, daß man eine Verbindung der allgemeinen Formel IIIn contrast to the known process, the new quinazolinones of the general formula I can be used smoothly and can be produced economically and in high yield and purity by making a compound of the general formula II
5555
6060
6565
in der n, R1 und R2 die vorstehende Bedeutung haben
C6H5
I
Cl C=Oin which n, R 1 and R 2 have the above meaning C 6 H 5
I.
Cl C = O
(III)(III)
NH-CO-C-X2 NH-CO-CX 2
in der Xi, X2 und X3 die vorstehende Bedeutung haben, mit einem Amin der allgemeinen Formel IVin which Xi, X 2 and X3 have the above meaning, with an amine of the general formula IV
NH,- C.H, „— NNH, - C.H, "- N
(IV)(IV)
in der n, Ri und R2 die vorstehende Bedeutung haben, oder dessen Salz in Gegenwart eines Lösungsmittels, wie Alkohol, glatt herstellen.in which n, Ri and R 2 have the above meanings, or prepare its salt smoothly in the presence of a solvent such as alcohol.
Die Chinazolinone der allgemeinen Formel I und deren Salze mit Säuren, wie Salzsäure, Bromwasserstoffsäure, Schwefelsäure, Phosphorsäure, Essigsäure, Maleinsäure, Fumarsäure, Weinsäure, Bernsteinsäure oder Citronensäure, sind wertvolle Arzneistoffe, insbesondere mit dämpfender Wirkung auf das Zentralnervensystem, antiphlogistischer und analgetischer Wirkung. Ferner fördern diese Verbindungen die Ausscheidung von Harnsäure, und sie haben antimikrobielle Aktivität. Die Verbindungen sind ferner wertvolleThe quinazolinones of the general formula I and their salts with acids, such as hydrochloric acid, hydrobromic acid, Sulfuric acid, phosphoric acid, acetic acid, maleic acid, fumaric acid, tartaric acid, succinic acid or citric acid, are valuable medicinal substances, especially with a depressant effect on the central nervous system, anti-inflammatory and analgesic effects. These compounds also promote excretion of uric acid and they have antimicrobial activity. The connections are also valuable
Zwischenprodukte zur Herstellung anderer Chinazolinderivate. Die Chinazolinone oder deren Salze der allgemeinen Formel I können parenteral oder oral in üblichen Verabreichungsformen, wie Tabletten, Dragees, Kapseln, Suspensionen, Lösungen oder Elixieren, verabfolgt werden.Intermediate products for the production of other quinazoline derivatives. The quinazolinones or their salts of general formula I can be administered parenterally or orally in usual forms of administration, such as tablets, coated tablets, capsules, suspensions, solutions or elixirs, administered.
VersuchsberichtTest report
In der nachstehenden Tabelle ist die antiphlogistische Wirkung einiger Verbindungen der Erfindung und einiger bekannter Verbindungen im Rattenpfotentest zusammengefaßtIn the table below is the anti-inflammatory activity of some compounds of the invention and some known compounds in the rat paw test summarized
TestverbindungTest connection
EDso,EDso,
mg/kg,mg / kg,
p.o.p.o.
LD»,LD »,
mg/kg,mg / kg,
p.o.p.o.
Verbindungen der ErfindungCompounds of the invention
3-(/?-Dimethylaminoäthyl)-4-phenyl-6-chlor-3,4-dihydro-2(l H)-chinazolinon, F. 173-J75°C3 - (/? - Dimethylaminoethyl) -4-phenyl-6-chloro-3,4-dihydro-2 (l H) -quinazolinone, 173-175 ° C
3-(ß-Diäthylaminoäthyl)-4-phenyl-6-chIor-3,4-dihydro-2(l H)-chinazolinon 3-()>-Dimethylaminopropyl)-4-phenyi-6-chbr-3,4-dihydro-2(l H)-chinazolinon 3{/?-MorpholinoäthyI)-4-phenyl-6-chlor-3,4-dihydro-2(l H)-chinazolinon3- (ß-Diethylaminoethyl) -4-phenyl-6-chloro-3,4-dihydro-2 (1 H) -quinazolinone 3 - ()> - Dimethylaminopropyl) -4-phenyi-6-chbr-3,4-dihydro-2 (1 H) -quinazolinone 3 {/? - Morpholinoethyl) -4-phenyl-6-chloro-3,4-dihydro-2 (1 H) -quinazolinone
Verbindungen aus der DT-OS 19 32 396Connections from DT-OS 19 32 396
l-Methyl-3-lt^-diäthylaminoäthyl)-4-phenyl-6-chlor-3,4-dihydro-2(l H)-chinazolinon 1 -Äthiyl-3-(ß-diäthylaminoäthyl)-4-phenyl-6-ch!or-3,4-dihydro-2( 1 H)-chinazolinonl-methyl-3-lt ^ -diethylaminoethyl) -4-phenyl-6-chloro-3,4-dihydro-2 (l H) -quinazolinone 1-Ethiyl-3- (ß-diethylaminoethyl) -4-phenyl-6-chloro-3,4-dihydro-2 (1 H) -quinazolinone
HandekpräparatHand preparation
Mefenamsäure (N-(2,3-Dimethylphenyl)-anthranilsäure) 180Mefenamic acid (N- (2,3-Dimethylphenyl) anthranilic acid) 180
200 250 200200 250 200
>400 >400> 400> 400
>400> 400
>1500> 1500
1500 >1500 >15001500> 1500> 1500
>1500 >1500> 1500> 1500
11001100
Die Beispiele erläutern die Erfindung. Beispiel 1The examples illustrate the invention. example 1
Ein Gemisch von 11,31g 2-Trichloracetamido-5-chlorbenzophenon, 5,3 g /?-Dimethylaminoäthylamin und 50 ml Dimethylsulfoxid wird 3 Stunden bei 90° C gerührt Nach dem Abkühlen wird das Reaktionsgemisch in 300 ml Wasser gegossen und das erhaltene Gemisch mit Chloroform exirahiert Die Chloroformschicht wird mit Wasser gewascnen und mit wasserfreiem Natriumsulfat getrocknet. Das Lösungsmittel wird unter vermindertem Druck abdestilliert und der Rückstand mit 30 ml Diäthyiäther versetzt Die so erhaltenen Kristalle werden abfiltriert, mit Diäthyiäther gewaschen und getrocknet. Es werden 8,34 g N1N-Dimethyl-N'-^-trichloracetamido-S-chlor-a-phenylbenzyliden)-äthylendiamin erhalten.A mixture of 11.31 g of 2-trichloroacetamido-5-chlorobenzophenone, 5.3 g /? - dimethylaminoethylamine and 50 ml of dimethyl sulfoxide is stirred for 3 hours at 90 ° C. After cooling, the reaction mixture is poured into 300 ml of water and the resulting mixture with Chloroform extracted. The chloroform layer is washed with water and dried with anhydrous sodium sulfate. The solvent is distilled off under reduced pressure and 30 ml of dietary ether are added to the residue. The crystals thus obtained are filtered off, washed with dietary ether and dried. It will be 8.34 g of N 1 N-dimethyl-N '- ^ - trichloroacetamido-S-chloro-a-phenylbenzyliden) -ethylenediamine obtained.
Eine Suspension von 8,18 g der erhaltenen Verbindung und 13 g Natriumborhydrid in 80 ml Dimethylformamid wird 3 Stunden auf 60°C erhitzt. Das Reaktionsgemisch wird nach und nach unter Eiskühlung in 400 ml verdünnte Salzsäure gegeben und .das erhaltene Gemisch mit verdünnter Natronlauge alkalisiert. Der so erhaltene Niederschlag wird abfiltriert, mit Wasser gewaschen und getrocknet. Es werden 5,0 g 3 - (ß -Dimethylaminoäthyl) - 4 - phenyl - 6 - chlor - 3,4 - di nyd.-o-2(lH)-chinazolinon erhalten. Nach dem Umkristallisieren aus Isopropanol werden feine farblose Kristalle mit einem F. von 173 bis 175°C erhallen.A suspension of 8.18 g of the compound obtained and 13 g of sodium borohydride in 80 ml of dimethylformamide is heated to 60 ° C. for 3 hours. The reaction mixture is gradually poured into 400 ml of dilute hydrochloric acid while cooling with ice, and the mixture obtained is made alkaline with dilute sodium hydroxide solution. The precipitate obtained in this way is filtered off, washed with water and dried. 5.0 g of 3 - (β- dimethylaminoethyl) -4-phenyl-6-chloro-3,4-di nyd.-o-2 (1H) -quinazolinone are obtained. After recrystallization from isopropanol, fine colorless crystals with a mp of 173 to 175 ° C are obtained.
Gemäß Beispiel 1 werden folgende Chinazolinone hergestellt:According to Example 1, the following quinazolinones are produced:
3-(j9-Diäthylaminoäthyl)-4-phenyl-6-chlor-3,4-dihydro-2(l H)-chinazolinon, F. 182,5 bis 183,50C;3- (j9-diethylaminoethyl) -4-phenyl-6-chloro-3,4-dihydro-2 (l H) -quinazolinone, m.p. 182.5 to 183.5 0 C;
3-(}>-Dimethylaminopropyl)-4-phenyl-6-chlor-3,4-dihydro-2(l HJ-chinazolinon, F. 175 bis 1770C (Zersetzung); 3-(|9-Morphoünoäthyl)-4-phenyl-6-chlor-3,4-dihydro-2(l H)-chinazolinon, F. 186,5 bis 187,50C.3 - (}> - Dimethylaminopropyl) -4-phenyl-6-chloro-3,4-dihydro-2 (l HJ-quinazolinone, F. 175 to 177 0 C (decomposition); 3- (| 9-Morphoünoäthyl) - 4-phenyl-6-chloro-3,4-dihydro-2 (l H) -quinazolinone, m.p. 186.5 to 187.5 0 C.
Claims (1)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP147771A JPS4940476B1 (en) | 1971-01-19 | 1971-01-19 | |
| JP147771 | 1971-01-19 | ||
| JP3489771 | 1971-05-21 | ||
| JP3489771 | 1971-05-21 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| DE2166327A1 DE2166327A1 (en) | 1973-10-31 |
| DE2166327B2 DE2166327B2 (en) | 1976-07-29 |
| DE2166327C3 true DE2166327C3 (en) | 1977-03-31 |
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